United States Prevention, Pesticides EPA 739-R-07-006 Environmental Protection and Toxic Substances September 2007 Agency (7510P)

Reregistration Eligibility Decision

for Glutaraldehyde

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES

CERTIFIED MAIL

Dear Registrant:

This is to inform you that the Environmental Protection Agency (hereafter referred to as EPA or the Agency) has completed its review of the available data and public comments received related to the preliminary risk assessments for the antimicrobial glutaraldehyde. The Reregistration Eligibility Decision (RED) for glutaraldehyde was approved on September 28, 2007. Public comments and additional data received were considered in this decision.

Based on its review, EPA is now publishing its Reregistration Eligibility Decision (RED) and risk management decision for glutaraldlehyde and its associated human health and environmental risks. A Notice of Availability will be published in the Federal Register announcing the publication of the RED.

The RED and supporting risk assessments for glutaraldehyde are available to the public in EPAs Pesticide Docket EPA-HQ-OPP-2007-0364 at: www.regulations.gov.

The glutaraldehyde RED was developed through EPAs public participation process, published in the Federal Register on September 10, 2004, which provides opportunities for public involvement in the Agencys pesticide tolerance reassessment and reregistration programs. The public participation process encourages robust public involvement starting early and continuing throughout the pesticide risk assessment and risk mitigation decision making process. The public participation process encompasses full, modified, and streamlined versions that enable the Agency to tailor the level of review to the level of refinement of the risk assessments, as well as to the amount of use, risk, public concern, and complexity associated with each pesticide. Using the public participation process, EPA is attaining its strong commitment to both involve the public and meet statutory deadlines.

Please note that the glutaraldehyde risk assessment and the attached RED document concern only this particular pesticide. This RED presents the Agencys conclusions on the dietary, occupational, residential and ecological risks posed by exposure to glutaraldehyde alone. This document also contains both generic and product-specific data that the Agency intends to require in Data Call-Ins (DCIs). Note that DCIs, with all pertinent instructions, will be sent to registrants at a later date. Additionally, for product-specific DCIs, the first set of required responses will be due 90 days from the receipt of the DCI letter. The second set of required responses will be due eight months from the receipt of the DCI letter.

Table of Contents

Glutaraldehyde Reregistration Team i

Glossary of Terms and Abbreviations... ii

Abstract........ iv

I. Introduction.. 1

II. Chemical Overview. ... 3

A. Regulatory History.. ... 3

B. Chemical Identification ... 3

C. Use Profile... 4

III. Summary of Glutaraldehyde Risk Assessments 6

A. Human Health Risk Assessment... 6

1. Toxicity of Glutaraldehyde 6

2. FQPA Safety Factor 12

3. Population Adjusted Dose (PAD)... 12

a. Acute PAD 12

b. Chronic PAD 12

4. Dietary Exposure Assumptions.. 13

5. Dietary Risk Assessment. 15

a. Food/Feed Contact Surfaces, Agricultural 18

Commodities..

b. Other Dietary Risks

c. Dietary Risk from Drinking Water .. 18

6. Residential Risk Assessment... 18

a. Residential Toxicity..... 18

b. Comparison to Other Endpoints.... 19

c. Residential Handlers.. .... 20

i. Summary of Registered Uses. . 20

ii. Exposure Assumptions.... 21

ii. Risk Assessment... 21

d. Residential Post-Application Assessment 24

i. Exposure Assessment. . 24

ii. Risk Characterization..... 25

7. Aggregate Risk. 25

8. Occupational Risk... 25

a. Occupational Toxicity. 25

b. Occupational Exposure Assumptions 25

c. Occupational Handler Exposures 26

d. Occupational Risk Assessment. 30

i. Professional Painting. . 30

ii. Surface Disinfection. .. 31

e. Occupational Post-application Risk Summary. 33

i. Fogging Assessment. 33

ii. Metal Working Fluid Assessment. 34

9. Human Incident Data.... 36

B. Environmental Risk Assessment.. 37

1. Environmental Fate and Transport... 37

a. Bioaccumulation in Aquatic Organisms 38

2. Ecological Risk. 38

a. Environmental Toxicity...... 38

b. Ecological Exposure and Risk .. 50

i. Down the Drain Model 52

c. Risk to Listed Species.. 54

IV. Risk Management, Reregistration, and Tolerance Reassessment Decision 56

A. Determination of Reregistration Eligibility. 56

B. Public Comments and Responses.. 56

C. Regulatory Position 57

1. Food Quality Protection Act Findings... 57

a. Determination of Safety to U.S. Population.. 57

b. Determination of Safety to Infants and Children. 57

c. Endocrine Disruptor Effects.. 58

d. Cumulative Risks. 58

D. Regulatory Rationale.. 58

1. Human Health Risk Management. 59

a. Residential Risk Mitigation 59

i. Handler Risk Mitigation . 59

ii. Post-Application Risk Mitigation.. 59

b. Occupational Risk Mitigation 60

i. Handler Risk Mitigation . 60

ii. Post-Application Risk Mitigation.. 60

2. Environmental Risk Management..... 61

3. Other Labeling Requirements 61

4. Listed Species Considerations.... 61

a. The Endangered Species Act.. 61

b. General Risk Mitigation..... 62

V. What Registrants Need to Do 63

A. Manufacturing-Use Products 65

1. Additional Generic Data Requirements 65

2. Labeling for Technical and Manufacturing Use Products.. 65

B. End-Use Products... 65

1. Additional Product-Specific Data Requirements......... 65

2. Labeling for End-Use Products.. 65

a. Label Changes Summary Table. 66

VI. Appendices. 69

A. Table of Use Patterns for Glutaraldehyde .. 70

B. Table of Generic Data Requirements and Studies Used to Make the 91

Reregistration Decision.....................

C. Technical Support Documents.. 99

D. Bibliography Citations... 101

E. Generic Data Call-In.. 121

F. Product Specific Data Call-In 122

G. Batching of End-Use Products.. 123

H. List of All Registrants Sent the Data Call-In... 124

I. List of Available Forms... 125

Glutaraldehyde Reregistration Team

Health Effects Risk Assessment Timothy McMahon Najm Shamim Timothy Dole Timothy Leighton Jonathan Chen Elissa Reaves

Ecological Risk Assessment Rick Petrie

Environmental Fate Risk Assessment Srinivas Gowda

Risk Management Michelle Centra Diane Isbell

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GLOSSARY OF TERMS AND ABBREVIATIONS

a.i. Active Ingredient aPAD Acute Population Adjusted Dose APHIS Animal and Plant Health Inspection Service ARTF Agricultural Re-entry Task Force BCF Bioconcentration Factor CDC Centers for Disease Control CDPR California Department of Pesticide Regulation CFR Code of Federal Regulations ChEI Cholinesterase Inhibition CMBS Carbamate Market Basket Survey cPAD Chronic Population Adjusted Dose CSFII USDA Continuing Surveys for Food Intake by Individuals CWS Community Water System DCI Data Call-In DEEM Dietary Exposure Evaluation Model DL Double layer clothing {i.e., coveralls over SL} DWLOC Drinking Water Level of Comparison EC Emulsifiable Concentrate Formulation EDSP Endocrine Disruptor Screening Program EDSTAC Endocrine Disruptor Screening and Testing Advisory Committee EEC Estimated Environmental Concentration. The estimated pesticide concentration in an

environment, such as a terrestrial ecosystem. EP End-Use Product EPA U.S. Environmental Protection Agency EXAMS Tier II Surface Water Computer Model FDA Food and Drug Administration FFDCA Federal Food, Drug, and Cosmetic Act FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FOB Functional Observation Battery FQPA Food Quality Protection Act FR Federal Register GL With gloves GPS Global Positioning System HIARC Hazard Identification Assessment Review Committee IDFS Incident Data System IGR Insect Growth Regulator IPM Integrated Pest Management RED Reregistration Eligibility Decision LADD Lifetime Average Daily Dose LC50 Median Lethal Concentration. Statistically derived concentration of a substance expected to cause

death in 50% of test animals, usually expressed as the weight of substance per weight or volume of water, air or feed, e.g., mg/l, mg/kg or ppm.

LCO Lawn Care Operator LD50 Median Lethal Dose. Statistically derived single dose causing death in 50% of the test animals

when administered by the route indicated (oral, dermal, inhalation), expressed as a weight of substance per unit weight of animal, e.g., mg/kg.

LOAEC Lowest Observed Adverse Effect Concentration LOAEL Lowest Observed Adverse Effect Level LOC Level of Concern LOEC Lowest Observed Effect Concentration mg/kg/day Milligram Per Kilogram Per Day MOE Margin of Exposure MP Manufacturing-Use Product MRID Master Record Identification (number). EPAs system of recording and tracking studies

submitted. MRL Maximum Residue Level

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N/A Not Applicable NASS National Agricultural Statistical Service NAWQA USGS National Water Quality Assessment NG No Gloves NMFS National Marine Fisheries Service NOAEC No Observed Adverse Effect Concentration NOAEL No Observed Adverse Effect Level NPIC National Pesticide Information Center NR No respirator OP Organophosphorus OPP EPA Office of Pesticide Programs ORETF Outdoor Residential Exposure Task Force PAD Population Adjusted Dose PCA Percent Crop Area PDCI Product Specific Data Call-In PDP USDA Pesticide Data Program PF10 Protection factor 10 respirator PF5 Protection factor 5 respirator PHED Pesticide Handlers Exposure Data PHI Pre-harvest Interval ppb Parts Per Billion PPE Personal Protective Equipment PRZM Pesticide Root Zone Model RBC Red Blood Cell RED Reregistration Eligibility Decision REI Restricted Entry Interval RfD Reference Dose RPA Reasonable and Prudent Alternatives RPM Reasonable and Prudent Measures RQ Risk Quotient RTU (Ready-to-use) RUP Restricted Use Pesticide SCI-GROW Tier I Ground Water Computer Model SF Safety Factor SL Single layer clothing SLN Special Local Need (Registrations Under Section 24C of FIFRA) STORET Storage and Retrieval TEP Typical End-Use Product TGAI Technical Grade Active Ingredient TRAC Tolerance Reassessment Advisory Committee TTRS Transferable Turf Residues UF Uncertainty Factor USDA United States Department of Agriculture USFWS United States Fish and Wildlife Service USGS United States Geological Survey WPS Worker Protection Standard

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ABSTRACT

The Environmental Protection Agency (EPA or the Agency) has completed the human health and environmental risk assessments for glutaraldehyde and is issuing its risk management decision. The risk assessments, which are summarized below, are based on the review of the required target database supporting the use patterns of currently registered products and additional information received through the public docket. After considering the risks identified in the revised risk assessments, comments received, and mitigation suggestions from interested parties, the Agency developed its risk management decision for uses of glutaraldehyde that pose risks of concern. As a result of this review, EPA has determined that glutaraldehyde -containing products are eligible for reregistration, provided that risk mitigation measures are adopted and labels are amended accordingly. That decision is discussed fully in this document.

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I. Introduction

The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended in 1988 to accelerate the reregistration of products with active ingredients registered prior to November 1, 1984 and amended again by the Pesticide Registration Improvement Act of 2003 to set time frames for the issuance of Reregistration Eligibility Decisions. The amended Act calls for the development and submission of data to support the reregistration of an active ingredient, as well as a review of all submitted data by the U.S. Environmental Protection Agency (EPA or the Agency). Reregistration involves a thorough review of the scientific database underlying a pesticides registration. The purpose of the Agencys review is to reassess the potential hazards arising from the currently registered uses of the pesticide; to determine the need for additional data on health and environmental effects; and to determine whether or not the pesticide meets the no unreasonable adverse effects criteria of FIFRA.

On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) was signed into law. This Act amends FIFRA to require tolerance reassessment. The Agency has decided that, for those chemicals that have tolerances and are undergoing reregistration, the tolerance reassessment will be initiated through this reregistration process. The Act also required that by 2006, EPA must review all tolerances in effect on the day before the date of the enactment of the FQPA. FQPA also amends the Federal Food, Drug, and Cosmetic Act (FFDCA) to require a safety finding in tolerance reassessment based on factors including consideration of cumulative effects of chemicals with a common mechanism of toxicity. This document presents the Agencys revised human health and ecological risk assessments; and the Reregistration Eligibility Decision (RED) for glutaraldehyde.

Glutaraldehyde is a disinfectant, sanitizer, biocide, fungicide, microbiocide, tuberculocide, and virucide antimicrobial chemical. As an antimicrobial agent, glutaraldehyde is applied to various sites, including food handling and food storage establishments such as commercial egg hatcheries, poultry/livestock equipment and processing premises, animal feeding and watering equipment; commercial/industrial buildings and trucks, construction materials, and laundry equipment; oil recovery drilling muds and secondary oil recovery injection water; metalworking fluids; commercial/industrial evaporative condensers and heat exchanger water systems; hospital, veterinary and laboratory premises/equipment; non-critical hospital plastic and rubber items; industrial coatings; and in the manufacture of a variety of materials as a preservative: cleaners, adhesives, paper and paperboard, water based coatings, latex paints, inks and dyes. Glutaraldehyde-containing products are also approved for use in aquatic areas such as ponds, flood water, and sewage water. It is not registered for any direct food uses.

The Agency has concluded that the special hazard-based FQPA Safety Factor should be removed (reduced to 1x) for glutaraldehyde based on the following: (1) the toxicology data base is complete with respect to assessing the increased susceptibility to infants and children as required by FQPA; (2) there is no concern for developmental neurotoxicity resulting from exposure to in the rat and rabbit prenatal developmental studies and 2-generation reproduction study; (3) there is no evidence of increased susceptibility to the fetus following in utero exposure in the prenatal developmental toxicity studies or to the offspring when adults are exposed in the two-generation reproduction study; and (4) the risk assessment does not underestimate the potential exposure for infants and children.

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Risks summarized in this document are those that result from the use of the active ingredient glutaraldehyde. The Food Quality Protection Act (FQPA) requires that the Agency consider available information concerning the cumulative effects of a particular pesticides residues and other substances that have a common mechanism of toxicity. The reason for consideration of other substances is due to the possibility that low-level exposures to multiple chemical substances that cause a common toxic effect by a common toxic mechanism could lead to the same adverse health effect that would occur at a higher level of exposure to any of the substances individually. Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding for glutaraldehyde and any other substances. Glutaraldehyde does not appear to produce a toxic metabolite produced by other substances. For the purposes of this action, therefore, EPA has not assumed that glutaraldehyde has a common mechanism of toxicity with other substances. For information regarding EPAs efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPAs Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPAs website at http://www.epa.gov/pesticides/cumulative.

This document presents the Agencys decision regarding the reregistration eligibility of the registered uses of glutaraldehyde. In an effort to simplify the RED, the information presented herein is summarized from more detailed information which can be found in the technical supporting documents for glutaraldehyde referenced in this RED. The revised risk assessments and related addenda are not included in this document, but are available in the Public Docket at http://www.regulations.gov (Docket ID #EPA-HQ-OPP-2007-0364).

This document consists of six sections. Section I is the introduction. Section II provides a chemical overview, a profile of the use and usage of Glutaraldehyde, and its regulatory history. Section III, Summary of Glutaraldehyde Risk Assessments, gives an overview of the human health and environmental assessments based on the data available to the Agency. Section IV, Risk Management, Reregistration, and Tolerance Reassessment Decision, presents the reregistration eligibility and risk management decisions. Section V, What Registrants Need to Do, summarizes the necessary label changes based on the risk mitigation measures outlined in Section IV. Finally, the Appendices list all use patterns eligible for reregistration, bibliographic information, related documents and how to access them, and Data Call-In (DCI) information.

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II. Chemical Overview

A. Regulatory History

The first product containing glutaraldehyde was registered on March 5, 1963. This reregistration case consists of a single pc code, 043901. There are currently 60 active products and two pending registrations for antimicrobial pesticide products containing glutaraldehyde as an active ingredient registered under Section 3 of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA).

B. Chemical Identification

1. Chemical Identity of Glutaraldehyde:

Chemical Name: 1, 5 Pentanedial

Chemical Family: Aldehyde

Common/Trade Name: Glutaraldehyde, Ucarcide 250, Glutaral

CAS Number: 111-30-8

Molecular Formula: C5H8O2

Chemical Structure:

OHC-CH2-CH2-CH2-CHO

Table 1. Chemical Characteristics for Technical Grade Active Ingredient Glutaraldehyde Chemical Characteristics

Molecular Weight 100.11 Color Colorless Odor Sharp and pungent Physical State Liquid/Pale Yellow Liquid Specific Gravity 1.13 at 20 oC Dissociation Constant Not applicable pH 3.1-4.5 / 3.5 Stability Stable for extended period of time at proper conditions Melting Point Not applicable to a liquid. The freezing point is

-18 o C to -21.2 o C. Boiling Point 100.7 oC at 760 mm Hg / 95 oC Water Solubility 51.3 g/L Octanol-Water Partition constant (Log KOW)

-0.18

Vapor Pressure 17 mm Hg @ 20 oC 11.5 mm Hg 20 mm Hg

Henrys Law Constant 2.4 x 10 -8 atm-m3 / mol Half Life (in air) 3.0 hours Oxidation/Reduction Not applicable. Technical grade active ingredient does not

contain any oxidizing or reducing agents Flammability Not reported

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Chemical Characteristics Explodability Technical grade active ingredient is not explosive Viscosity 20.15 cp @ 20 oC/2 cps @ 20 oC Miscibility Miscible Corrosion Characteristic Not applicable Dielectric Breakdown Voltage Not established for technical grade active ingredient

C. Use Profile

The following is information on the currently registered uses of Glutaraldehyde products and an overview of use sites and application methods. A detailed table of the uses of Glutaraldehyde eligible for reregistration is contained in Appendix A.

Type of Pesticide: Algaecide Bacteriocide

Fungicide

Summary of Use:

Products containing glutaraldehyde as an active ingredient are intended for use in agricultural, food handling, commercial/institutional/ industrial, residential and public access, and medical settings (Use Site Categories I, II, III, IV and V, respectively), as well as a materials preservative for a variety of products (Use Site Category VII) and as an industrial processes and water systems treatment (Use Site Category X). Some examples of uses are listed below, for a detailed use description please refer to Appendix A.

Agricultural Premises and Equipment: Glutaraldehyde is used for egg sanitation, in hatcheries, setters and chick processing facilities; in animal housing buildings; on farm equipment, trays, racks, carts, chick boxes, cages, trucks, vehicles, and other hard surfaces.

Commercial/Institutional/Industrial: Glutaraldehyde is used in janitorial, commercial, and industrial facilities; in laboratories, biomedical research facilities, nursing homes, veterinary hospitals and facilities, on cages, urinals, and hard surfaces; and in the treatment of medical waste, human waste and animal waste.

Residential and Public Access: Glutaraldehyde is used in applications to treat hard surfaces in public access premises.

Materials Preservatives: Glutaraldehyde is used in industrial, institutional, and consumer in-can process and products; concrete admixtures; and reverse osmosis membranes.

Medical Premises and Equipment: Glutaraldehyde is used to disinfect hospital, medical, and dental office equipment/ premises/surfaces; and solid and liquid medical waste.

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Industrial Processes and Water Systems: Glutaraldehyde is used in oil-storage tanks; water floods; drilling muds, drilling, completion, and workover fluids; packer fluids; gas-production and transmission pipe systems; gas storage wells and systems; hydrotesting; pipeline pigging and scraping operations; paper mills and paper mill process water systems; pigments, filler slurries and water based coatings for paper and paperboard; metalworking fluids; water-based conveyor lubricants; air washer and industrial scrubbing; systems/recirculating cooling and process water systems; service water and auxiliary systems; heat transfer systems; industrial waste-water systems; and sugar beet mills and process water systems.

Target Pests: Deterioration/spoilage bacteria, fungi (coatings, leather, metal working coolants), mildew, mold, pseudomonas spp.

Formulation Types of Glutaraldehyde:

Soluble concentrates, ready-to-use solutions, impregnated materials, water soluble packages, and microencapsulated preparations (medical waste). Glutaraldehyde is not available as a neat, undiluted chemical. However, it is commercially available as 4%, 15%, 25%, 45%, and 50% (v/v) aqueous solutions.

Method and Rates of Application:

The methods and rates of application for Glutaraldehyde-containing products vary greatly depending on use site. Please refer to Appendix A for more detailed application rates for each use site and methods of application..

Use Classification: General use.

Manufactures (Technical Grade Active Ingredient):

The Dow Chemical Company

BASF Corporation

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III. Summary of Glutaraldehyde Risk Assessments

The purpose of this summary is to assist the reader by identifying the key features and findings of these risk assessments and to help the reader better understand the conclusions reached in the assessments. The human health and ecological risk assessment documents and supporting information listed in Appendix C were used to formulate the safety finding and regulatory decision for glutaraldehyde. While the risk assessments and related addenda are not included in this document, they are available from the OPP Public Docket EPA-HQ-OPP-20070364, and may also be accessed from www.regulations.gov. Hard copies of these documents may be found in the OPP public docket. The OPP public docket is located in Room S-4900, One Potomac Yard, 2777 South Crystal Drive, Arlington, VA 22202, and is open Monday through Friday, excluding Federal holidays, from 8:30 a.m. to 4:00 p.m.

The Agencys use of human studies in the glutaraldehyde risk assessment is in accordance with the Agency's Final Rule promulgated on January 26, 2006, related to Protections for Subjects in Human Research, which is codified in 40 CFR Part 26.

A. Human Health Risk Assessment

1. Toxicity of Glutaraldehyde

A brief overview of the toxicity studies used for determining endpoints in the risk assessment is outlined below in Table 1. Further details on the toxicity of glutaraldehyde can be found in the supporting toxicology documents listed in Appendix C. These documents are available on the Agencys website in the EPA Docket at: http://www.regulations.gov (Docket ID #EPA-HQ-OPP-2007-0364).

The Agency has reviewed all toxicity studies submitted for glutaraldehyde as well as open literature data and determined that the toxicological database is substantially complete for the purpose of reregistration. Most of these studies have been submitted to support the guideline requirements for toxicity testing.

Major features of the toxicology profile are presented below. Glutaraldehyde exhibits low acute dermal and inhalation toxicity (Toxicity Category III and IV, respectively). However, it is highly toxic via the acute oral route (Toxicity Category II) and highly irritating to the eyes and skin (Toxicity Category I). In a submitted local lymph node assay, glutaraldehyde produced a dose-related increase in proliferative activity, indicating that it is a positive dermal sensitizer.

Table 2. Summary of Acute Toxicity Data for Glutaraldehyde Guideline Number

Study Type/ Test substance (% a.i.) MRID #(s) Results

Toxicity Category

870.1100 Acute Oral - Rat Glutaraldehyde (50% a.i.)

00011706 00164370

LD50 = 360 mg/kg (male) LD50 = 420 mg/kg (female) LD50 = 460 mg/kg (combined)

II

870.1200 Acute Dermal - Rabbit Glutaraldehyde (50.2%) 44691606 LD50 > 2000 mg/kg (combined) III

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Guideline Number

Study Type/ Test substance (% a.i.) MRID #(s) Results

Toxicity Category

870.1300 Acute Inhalation - Rat. 00060275 LC50 > 4.16 mg/L IV

870.2400 Primary Eye Irritation - Rabbit Glutaraldehyde ( 0.5%) 00117066

Corrosive at high concentrations, such as 50% a.i. I

870.2500 Primary Dermal Irritation - Rabbit Glutaraldehyde (50%) 00117061

Corrosive Primary Irritation Score (PIS) = 6.34 I

870.2600 Dermal Sensitization LLNA Assay in Mice 43330201 SI > 3 ; positive sensitizer N/A

Notes: LC = Lethal Concentration; LD = Lethal Dose; NA = Not Applicable

The doses and toxicological endpoints selected for the dietary exposure scenarios are summarized in Table 3 below:

Table 3. Dietary Toxicological Endpoints for Glutaraldehyde Exposure Scenario

Dose Used in Risk Assessment, UF

Special FQPA SF* and Level of Concern for

Risk Assessment

Study and Toxicological Effects

Acute Dietary (females 13-49)

No appropriate endpoints were identified that represent a single dose effect. Therefore, this risk assessment is not required.

Chronic Dietary (all populations)

NOAEL= 16.1 mg/kg/day

UF = 100 (10x inter-species extrapolation and intraspecies variation) FQPA SF = 1x

Chronic RfD = cPAD = 0.16 mg/kg/day

Carcinogenicity Study (drinking water) in the Rat (MRID 46212701)

LOAEL = 61 mg/kg/day based on increases in non-neoplastic lesions (squamous metaplasia, foreign body granuloma, pirulent inflammation) of the respiratory tract and erosion/ulceration in the mucosa of the glandular stomach.

Cancinogenicity In accordance with the EPA Final Guidelines for Carcinogen Risk Assessment (March 29, 2005), the Health Effects Divisions Carcinogenicity Assessment Review Committee concluded that glutaraldehyde was not likely to be carcinogenic to humans by any route of exposure.

Notes: UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c = chronic) RfD = reference dose

General Toxicity Observations

Developmental and Reproductive/Fertility Effects

Developmental toxicity studies conducted in rats and rabbits were available for glutaraldehyde. In a developmental toxicity study conducted in rabbits, a NOAEL of 15 mg/kg/day and a NOAEL of 45 mg/kg/day was established for maternal and developmental toxicity, respectively. For maternal toxicity, the LOAEL was based on maternal death (4/15 treatment-related), sharply decreased food consumption, markedly decreased body weight/ body weight gain, and increased incidence of soft stool, diarrhea, or no defecation. For developmental toxicity, the LOAEL is based on almost complete early resorption (1 surviving litter) and

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decreased body weight of 4 surviving fetuses. In two developmental (oral) toxicity studies conducted in the rat, NOAELs for maternal and developmental toxicity were greater than the highest doses tested (50 and 68 mg/kg/day, respectively) and therefore, LOAELs were not established.

Two-generation reproduction toxicity studies were submitted for glutaraldehyde. In the first study, a parental systemic toxicity and reproductive toxicity were not observed in rats at concentrations up to the highest dose tested, 1000 ppm. For pups in both generations, systemic/developmental toxicity was observed as decreased body weight gain on lactation days 14, 21, and 28; a NOAEL of 250 ppm and a LOAEL of 1000 ppm was established. In the second reproduction toxicity study, a parental systemic toxicity LOAEL of 76 mg/kg/day and 95.6 mg/kg/day and a NOAEL of 22.4 mg/kg/day and 28.7 mg/kg/day for males and females, respectively, based on decreased body weight, body weight gain, and food consumption, as well as macroscopic and microscopic changes in the glandular stomach. Adverse effects on reproductive performance and fertility effects were not observed at the highest doses tested, 76 mg/kg/day for males, 95.6 mg/kg /day for females. The offspring LOAEL is 76 mg/kg/day and 95.6 mg/kg /day and the NOAEL is 22.4 mg/kg/day and 28.7 mg/kg/day for males and females, respectively, based on decreased litter and pup weights.

Subchronic Toxicity

Several subchronic oral, dermal and inhalation toxicity studies were conducted with glutaraldehyde. In a range-finding (14-day) oral toxicity study in mice, no toxicities were observed and the NOAEL was established at the highest doses tested (257.4 and 327.6 mg/kg/day in males and females, respectively). In the 90-day subchronic oral toxicity study conducted in mice, glutaraldehyde was administered in drinking water and a NOAEL of 60.8 and 74.3 mg/kg/day for males and females, respectively was established based on a treatment-related increase in gastritis and possibly treatment-related decreases in urine volume and osmolality that occurred at a LOAEL of 199.8 and 238.1 mg/kg/day for males and females, respectively. In a combined 90-day oral (drinking water) subchronic and neurotoxicity study in rats, NOAELs of 52.9 and 71.5 mg/kg/day were established at the highest doses tested for males and females, respectively. A LOAEL was not established in this study and there were no observed neurotoxic effects. The 90-day oral (drinking water) toxicity study conducted in dogs established a NOAEL of 9.8 mg/kg/day based on increased incidence of vomiting in males and females that occurred at a LOAEL of 14.6 mg/kg/day.

Following a subchronic, 28-day dermal exposure, glutaraldehyde, caused dermal irritation (erythema and edema) and skin lesions (discoloration, acanthosis, hyperkeratosis, dermatitis, epidermitis and dermal fibrosis) in rats at the LOAEL of 100 mg/kg/day. The NOAEL was established at 50 mg/kg/day in this study.

In a 14-day subchronic inhalation toxicity study conducted in F344/N rats and B6C3F1 mice, animals were exposed to glutaraldehyde by whole-body inhalation. Toxicities observed at the LOAEL of 0.5 ppm (2.0 mg/m3) included histopathological changes in the nasal passages and turbinates (hyperplasia and squamous metaplasia), the larynx and trachea (inflammation, necrosis and squamous metaplasia), and the lung and bronchi (inflammation); the NOAEL was established at 0.16 ppm (0.7 mg/m3). In a longer duration (90-day) subchronic inhalation

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(whole-body) toxicity study conducted in same species, the NOAEL was established at 125 ppb (0.512 mg/m3) based on histopathological changes in the nasal and respiratory tract (hyperplasia, squamous metaplasia and inflammation of the nasoturbinate/septal epithelium, degeneration of the olfactory epithelium and squamous exfoliation of the nasal vestibule/anterior nares) observed at the LOAEL of 250 ppb (1.02 mg/m3). A second 90-day inhalation (whole-body) toxicity study conducted in F344 rats showed only decreased body weight gains throughout the study at 49.3 ppb and above.

Chronic Toxicity

Three chronic toxicity studies are available for glutaraldehyde, including three oral studies (two in the rat and one in the dog) and one chronic inhalation study in rats and mice. In the first oral (drinking water) toxicity study, the NOAEL was established at 500 ppm (15.4 and 23.2 mg/kg/day in males and females, respectively) based on decreased body weight in males, increased incidence of erosions and ulcers in the glandular stomach of both sexes and a slight increase in clear cell foci of the liver in males observed at the LOAEL of 2000 ppm (58.9 and 77.4 mg/kg/day in males and females, respectively). The second drinking water toxicity study toxicities that included slightly decreased body weight/body weight gain in males and decreased food consumption in males and females; the NOAEL was established at 50 ppm (17 and 25 mg/kg/day in males and females, respectively). In the dog drinking water toxicity study, no toxicities were observed and the NOAEL established in this study is the highest dose tested (500 ppm (15.6 mg/kg/day).

In the two-year chronic toxicity/carcinogenicity inhalation toxicity study conducted in F344/N rats and B6C3F1 mice, whole-body exposure to glutaraldehyde resulted in microscopic lesions (inflammation, hyperplasia, squamous metaplasia and hyaline degeneration of the epithelium) of the nose and respiratory tract observed at the LOAEL of 250 ppb (1.02 mg/m3; lowest dose tested) in rats and at the LOAEL of 62.5 ppb (0.26 mg/m3; lowest dose tested) in mice; the NOAEL was not established in either species. At the concentrations tested in this study, there was no evidence for carcinogenicity of glutaraldehyde in either rats or mice.

Neurotoxicity

The available toxicity data do no indicate neurotoxicity in rats exposed to glutaraldehyde by the oral (drinking water) route of administration.

Dietary

An acute dietary endpoint was not identified in the glutaraldehyde toxicology database because no effect observed could be attributed to a single dose effect. Therefore, an acute RfD was not calculated for glutaraldehyde.

The chronic RfD for glutaraldehyde is 0.16 mg/kg/day for all populations. The chronic RfD was established by using a NOAEL of 16.1 mg/kg/day, which is based on increases in nonneoplastic lesions (squamous metaplasia, foreign body granuloma, pirulent inflammation) of the respiratory tract and erosion/ulceration in the mucosa of the glandular stomach.observed at the LOAEL of 61 mg/kg/day in a carcinogenicity study conducted in rats. An uncertainty factor of 100

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(10x for inter-species extrapolation and 10x for intra-species variation) was applied to the selected endpoint.

Short-term Dermal The short-term dermal NOAEL is 50 mg/kg/day (2.5% @ 40 l/cm2 ;1000 g/cm2) based

on dermal irritation (erythema and edema) and skin lesions (discoloration, acanthosis, hyperkeratosis, dermatitis, epidermitis and dermal fibrosis) in rats observed at the LOAEL of 100 mg/kg/day in a 28-day dermal toxicity study. The target MOE, for the short-term dermal exposure is 10X (3x for inter-species extrapolation and 3x intra-species variation).

Short-term Inhalation

The short-term inhalation NOAEL is 0.7 mg/m3 based on histopathological changes in the nasal passages and turbinates (hyperplasia and squamous metaplasia), the larynx and trachea (inflammation, necrosis and squamous metaplasia), and the lung and bronchi (inflammation) observed at the LOAEL of 2.0 mg/m3 in a 14-day inhalation toxicity study conducted in mice and rats. The NOAEL value of 0.7 mg/m3 was converted to a human equivalent concentration of 0.041 and 0.014 mg/m3 for occupational and residential exposures, respectively. The target MOE, for the short-term inhalation exposure is 30 (3x for inter-species extrapolation and 10x for intra-species variation).

Intermediate-term Inhalation

The intermediate-term inhalation NOAEL is 0.512 mg/m3 based on histopathological changes in the nasal and respiratory tract (hyperplasia, squamous metaplasia and inflammation of the nasoturbinate/septal epithelium, degeneration of the olfactory epithelium and squamous exfoliation of the nasal vestibule/anterior nares) observed at the LOAEL of 1.02 mg/m3 in a 90day (whole-body) inhalation toxicity study conducted in rats and mice. The NOAEL value of 0.512 mg/m3 was converted to a human equivalent concentration of 0.03 and 0.01 mg/m3 for occupational and residential exposures, respectively. The target MOE, for the intermediate-term inhalation exposure is 30 (3x for inter-species extrapolation and 10x for intra-species variation).

Long-term Inhalation

The long-term inhalation LOAEL is 0.26 mg/m3 based on microscopic lesions (inflammation, hyperplasia, squamous metaplasia and hyaline degeneration of the epithelium) of the nose and respiratory tract observed in a two-year chronic inhalation (whole-body) toxicity study conducted in mice. A NOAEL value was not established. The LOAEL value of 0.26 mg/m3 was converted to a human equivalent concentration of 0.019 and 0.004 mg/m3 for occupational and residential exposures, respectively. The target MOE, for the long-term inhalation exposure is 300 (3x for inter-species extrapolation, 10x for intra-species variation and 10x for use of a LOAEL).

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Carcinogenicity Classification

The carcinogenic potential of glutaraldehyde was tested in several two-year rat studies via the inhalation and oral (drinking water) route of administration. By the inhalation route, there was no evidence of carcinogenicity for glutaraldehyde in either Fischer 344 rats or B6C3F1 mice. In a drinking water carcinogenicity study, Wistar rats showed no carcinogenic response to glutaraldehyde. However, a positive carcinogenic response was observed in a second oral (drinking water) carcinogenicity study conducted in Fischer 344 rats, a strain of rat known to be susceptible to development of large granular lymphocyte leukemia (LGLL). In female Fischer 344 rats, an increased incidence of LGLL was observed in this study. Although the highest dose tested showed a significant increase in LGLL tumor incidence, the lower doses gave no clear indication of a dose-response. In addition, comparison of the response at lower doses with historical control data showed that this tumor type in general has a wide variability of incidence even in untreated animals. Thus, the increased incidence of LGLL is not considered a treatment-related effect of glutaraldehyde. This conclusion is supported by the available experimental evidence that has not identified a clear etiology for LGLL in the rat. These data were reviewed by OPPs Carcinogenicity Assessment Review Committee (CARC) in February of 2006. The CARC classified glutaraldehyde as Not Likely to be Carcinogenic to Humans by any route of exposure.

Mutagenicity Potential

Based on the results of a battery of submitted mutagenicity studies as well as published literature, glutaraldehyde produced reverse gene mutations in Salmonella typhimurium, and showed positive responses for forward gene mutations in Chinese hamster (CHO) cell and mouse lymphoma cells . However, glutaraldehyde was not mutagenic at the HGPRT locus and was negative for chromosome aberration studies in CHO cells. Glutaraldehyde has produced inconsistent results in several in vitro tests. Consequently, these data results are considered equivocal. The negative results shown in sister chromatid (SCE) induction in CHO cells together with the no cell transformation occurring in an in vitro Syrian hamster embryo cells suggests that glutaraldehyde has limited mutagenic potential because of its high cytotoxicity. Therfore, glutaraldhyde is considered non mutagenic or genotoxic.

Endocrine Disruption Potential

EPA is required under the Federal Food Drug and Cosmetic Act (FFDCA), as amended by FQPA, to develop a screening program to determine whether certain substances (including all pesticide active and other ingredients) may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effects as the Administrator may designate. Following recommendations of its Endocrine Disruptor and Testing Advisory Committee (EDSTAC), EPA determined that there was a scientific basis for including, as part of the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone system. EPA also adopted EDSTACs recommendation that the Program include evaluations of potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA authority to require the wildlife evaluations. As the science develops and resources

11

allow, screening of additional hormone systems may be added to the Endocrine Disruptor Screening Program (EDSP). When the appropriate screening and/or testing protocols being considered under the Agencys Endocrine Disrupting Screening Program (EDSP) have been developed, glutaraldehyde may be subjected to additional screening and/or testing to better characterize effects related to endocrine disruption.

2. FQPA Safety Factor

The FQPA Safety Factor (as required by the Food Quality Protection Act of 1996) is intended to provide an additional 10-fold safety factor (10x), to protect for special sensitivity in infants and children to specific pesticide residues in food, drinking water, or residential exposures, or to compensate for an incomplete database. The Agency has concluded that the special hazard-based FQPA safety factor can be removed (i.e., reduced to 1x) for glutaraldehyde based on: (1) a complete toxicology data base with respect to assessing increased susceptibility to infants and children as required by FQPA; (2) a lack of evidence that glutaraldehyde will induce neurotoxic effects; (3) no evidence of increased susceptibility to the fetus following in utero exposure in the prenatal developmental toxicity studies; (4) no evidence of increased susceptibility to the offspring when adults are exposed in the two-generation reproduction study; and (5) the risk assessment does not underestimate the potential exposure for infants and children. Based on the analysis of submitted toxicity studies, the Agency determined that no special hazard-based FQPA Safety Factor was needed since there were no residual uncertainties for pre- and/or post-natal toxicity.

3. Population Adjusted Dose (PAD)

Dietary risk is characterized in terms of the Population Adjusted Dose (PAD), which reflects the reference dose (RfD), either acute or chronic, that has been adjusted to account for the FQPA Safety Factor (SF). This calculation is performed for each population subgroup. A risk estimate that is less than 100% of the acute or chronic PAD is not of concern. The Agency has conducted a dietary exposure and risk assessment for the use of glutaraldehyde as a hard surface cleaner, in animal premises and poultry premises( including hatcheries) and as a slimicide and materials preservative in pulp and paper manufacturing.

a. Acute PAD

An acute dietary assessment was not conducted for glutaraldehyde because no appropriate endpoints were identified in the toxicology database representative of a single dose effect.

b. Chronic PAD

Chronic dietary risk for glutaraldehyde is assessed by comparing chronic dietary exposure estimates (in mg/kg/day) to the chronic Population Adjusted Dose (cPAD). Chronic dietary risk is expressed as a percent of the cPAD. The cPAD is the chronic reference dose (0.16 mg/kg/day) modified by the FQPA safety factor. The cPAD was derived from a chronic oral (drinking water) toxicity study in rats in which the LOAEL (61 mg/kg/day) was determined. The glutaraldehyde cPAD is 0.16 mg/kg/day based on a reference dose of 0.16 mg/kg/day, which incorporates the FQPA safety factor (1x) for all populations.

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4. Dietary Risk Assumptions

The use of glutaraldehyde on food or feed contact surfaces, agricultural commodities, and in animal premises and poultry premises (including hatcheries) may result in pesticide residues in human food and therefore, pose a risk to human health. The use sites which are quantitatively assessed in this document are listed in Table 4 along with the registration numbers and the maximum application associated with each dietary exposure scenario (Table 3). These scenarios represent worst-case estimates of indirect food contact dietary exposure and include application to hard surfaces in food processing plants, application to adhesives used in papermaking, application to pigments and fillers used in papermaking, and application to papermill process water systems as a slimicide.

Table 4: Use Site Categories and Application Rates Scenario Product Labela (EPA

Registration No.) Method of

Application Maximum

Application Rateb (lb a.i./gal)

Label Notes Regarding Indirect of Direct Food

Contact

Hard non-porous surfaces in food processing plants (including chicken processing facilities)

71355-1 Coarse spray, mop, sponge

536 ppm ai

(1 gal product/ 200 gal water * 10^6 * 10.725 % ai)

Before using this product, all food products and packaging materials must be removed from the room or carefully protected

A potable water rinse is required for all surfaces that come into contact with food

Paper mills and associated process water systems (including treatment at beaters, broke chest pump, save-all tank, or whitewater tank)

464-692, 464-700 464-702, 464-708 1448-354, 1448-421 1448-422, 1448-423 1448-429, 1448-430 1448-431, 1677-206 33753-26, 33753-27 33753-30, 33753-31 67869-36

Intermittent or continuous feed methods

750 ppm ai (0.075% ai)

(50% ai * 3 lbs product / ton pulp or paper * 1 ton/ 2,000 lb * 10^6)

None

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Scenario Product Labela (EPA Registration No.)

Method of Application

Maximum Application Rateb

(lb a.i./gal)

Label Notes Regarding Indirect of Direct Food

Contact

Pigments and filler slurries for paper and paperboard

464-703, 464-708, 464-692, 1448-421, 1448-422, 1448-423, 1448-429, 1448-430, 1448-431, 1448-354 1677-206, 33753-26, 33753-27, 33753-30, 33753-31, 67869-36

Apply once during manufacturing

300 ppm ai

(50% ai * 600 ppm as product [based on slurry solids] in mixed slurry)

or

0.00030 lb ai/lb slurry or dry powder

(50% ai * 6 lb product/10,000 lb dry powder)

For Food and Non-Food Contact Paper and Paperboard

Sugar beet mills and process water systems (including treatment at diffuser, transport water pump, weir box, or diffuser feed water pump)

464-692, 1677-206, 33753-26, 33753-27, 33753-30, 33753-31

Intermittent or continuous feed methods

0.45 lb ai/ton sliced beet

(45% ai * 8.34 * 15.2 oz/ton sliced beet * 1 gal / 128 oz)

or

252 ppm ai

(45% ai * 560 ppm product)

None

Water based conveyor lubricants for use in brewery, juice, dairy, beverage, and food processing systems

464-692, 1677-206 33753-26, 33753-27 33753-31

Automatic feed system

300 ppm ai

(600 ppm product *50% ai)

Avoid contamination of food in application of this product

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Scenario Product Labela (EPA Registration No.)

Method of Application

Maximum Application Rateb

(lb a.i./gal)

Label Notes Regarding Indirect of Direct Food

Contact

Farm equipment and animal housing buildings (including poultry grow-out and laying houses): hard non-porous surfaces such as floors, walls, forks, shovels

And

Hatcheries: trays, racks, carts, chick boxes, cages, hatchers, settlers, chick processing facilities, hatchery humidity control equipment, and other hard surfaces

464-689, 464-696, 464689, 464-700, 464-702, 464-716, 464-715, 71355-1

Course sprayer, mop, sponge, immersion, fogging

0.0201 lb ai/gal

(12.8% ai * 8.34 lb ai/gal * 2.41 oz/gal * 1 gal/128 oz)

or

0.25% ai solution

"Sanitizing Non-food contact surfaces, farm, animal, and poultry housing facilities and equipment"

Thoroughly scrub treated feed racks, troughs, and other feeding and water appliances with soap or detergent and rinse with potable water before reuse

Egg Sanitization: hatching eggs

464-689, 464-696, 464689, 464-700, 464-702, 464-716, 464-715

Immersion (10 to 15 seconds) or fogging/ atomizing

Immersion 0.0091 lb ai/gal

(14% ai * 8.34 lb ai/gal * 1 oz/gal * 1 gal/128 oz)

Fogging/Atomizing 0.25% ai solution

For treating hatching eggs only

5. Dietary Risk Assessment

a. Food/Feed Contact Surfaces, Agricultural Commodities and Animal/Poultry Premises

Chronic dietary risk assessments were conducted for the use of glutaraldehyde on food or feed contact surfaces, agricultural commodities, and in animal and poultry premises including hatcheries. For all scenarios quantitatively evaluated, none of the calculated % cPAD values exceeded 100%. Therefore, the Agency has no risk concerns from the indirect food uses of glutaraldehdye, as indicated by the rates of application rates and the dietary exposure scenarios quantitatively assessed in this document.

In the absence of data for residues of glutaraldehyde on treated food and feed contact surfaces, the Agency has estimated residue levels that may occur in food using maximum

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application rates from product labels and a variety of FDA models and assumptions. Using the residue estimates, Estimated Daily Intake (EDI) (mg/person/day) and Dietary Daily Dose (DDD) (mg/kg/day) values were calculated for each scenario. These daily estimates were conservatively used to assess chronic dietary risks by calculating the % cPAD (chronic population-adjusted dose). Risks exceed the Agencys level of concern when the % cPAD exceeds 100%.

For application to hard surfaces in food processing plants, the % cPAD values assuming a 10% transfer rate from the treated hard surface to food (from FDA Sanitizing Guidelines) were 0.96% for adult males, 1.12% for adult females, and 4.47% for children. Assuming a 100% transfer rate, the % cPADs were 9.57 for adult males, 11.17% for adult females, and 44.67% for children (Table 5).

Table 5. Calculated EDIs, DDDs and % cPADs for Hard Surfaces (Countertop) in Food Processing Plants

Exposure Group Transfer Rate of 10% Transfer Rate of 100%

EDI (mg/p/d)

DDD (mg/kg/d)

% cPADa EDI (mg/p/d)

DDD (mg/kg/d)

% cPADa

Adult males 0.112 0.00160 1.00 1.12 0.0160 10.0 Adult females 0.112 0.00187 1.12 1.12 0.0187 11.7

Children 0.112 0.00747 4.67 1.12 0.0747 46.7 a. % cPAD = exposure (DDD) / ( cPAD) x 100. cPAD = 0.16 mg/kg/day

Glutaraldehyde can be used as a general preservative in food-contact adhesives and mineral slurries used in papermaking. Glutaraldehyde is cleared for use by the Food & Drug Administration (FDA) as an adhesive component (21 CFR 175.105). For application to adhesives in papermaking, the % cPAD values were 0.00019% for adult males, 0.00022% for adult females, and 0.00044% for children (Table 6).

Table 6. Calculated EDIs, DDDs, and %cPADs for Adhesives Used in Papermaking

Exposure Group EDI (mg/day) DDD (mg/kg/day) % cPADa

Adult males 2.10E-05 3.00E-07 0.00019 Adult females 2.10E-05 3.50E-07 0.00022

Children 1.05E-05 7.00E-07 0.00044 a. % cPAD = exposure (DDD) / (cPAD) x 100

The Agency has used the FDA model to estimate the residue level of glutaraldehyde that will be present in treated paper from its use as a slimicide and which could then migrate into food exposed to the treated paper. The calculated EDIs, DDDs and %cPADs for glutarladehyde use as a slimicide are presented in Table 7. Glutaraldehyde is also cleared for use by the FDA as a slimicide (21 CFR 176.300) with no dosage limitations.

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Table 7. Calculated EDIs, DDDs, and %cPADs for Slimicides Used in Papermaking

Exposure Group EDI (mg/day) DDD (mg/kg/day) % cPADa

Adult males 0.021 0.0003 0.185 Adult females 0.021 0.00035 0.219

Children 0.0105 0.0007 0.438 a. % AD = exposure (DDD) / (cPAD) x 100

Glutaraldehyde-containing products are used to inhibit the growth of spoilage microorganisms in pigments and filler slurries for food contact paper during their manufacture, storage, and distribution. The calculated EDIs, DDDs and %cPADs for glutarladehyde use in fillers for papermaking are presented in Table 8.

Table 8. Calculated EDIs, DDDs, and %cPADs for Filler Used in Papermaking

Exposure Group EDI (mg/day) DDD (mg/kg/day) % cPAD a

Adult males 0.0015 0.000022 0.014 Adult females 0.0015 0.000026 0.016

Children 0.00075 0.000051 0.032 a. % AD = exposure (DDD) / (cPAD) x 100

Many glutaraldehyde product labels list directions for both application to food contact paper for the filler use and a non-food contact paper coating use. Presumably, both uses can be made to the same paper and therefore, addititve result exposures to glutaraldehyde from the use of the treated paper on food. The Agency considers all paper uses as having the potential for food contact. Thus, the EDIs, DDDs and %cPADs were calculated for coatings used in papermaking (Table 9).

Table 9. Calculated EDIs, DDDs, and %cPADs for Coatings Used in Papermaking

Exposure Group EDI (mg/day) DDD (mg/kg/day) % cPAD a

Adult males 0.045 0.00064 0.4 Adult females 0.045 0.00075 0.47

Children 0.0225 0.0015 0.94 a. % AD = exposure (DDD) / (cPAD) x 100

Dietary exposures from general agricultural premise use (hard surfaces such as floors and walls in barns and animal houses, empty watering/feed troughs, animal halters, ropes and forks), poultry hatcheries (including egg sanitization) and poultry laying facilities (residues on egg shells) are expected to be much lower than the dietary exposures resulting from representative surface disinfectant and sanitizing uses that were quantitatively assessed. In the absence of any adverse data at this time, the Agency has no concerns for the agricultural uses listed.

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b. Other Dietary Risks

Glutaraldehyde can also be used on conveyor belts in food processing plants. This use was determined to be a non food-contact use and, therefore, was not quantitatively assessed.

The use of glutaraldehyde-containing products in sugar beet mills and water systems for processing of sugarcane or sugar beet is considered a food use. However, glutaraldehyde may be safely used as a single additive for controlling microorganisms in sugar beet mills at a maximum level of 250 ppm in terms of the weight of the raw cane or raw beet (21 CFR 173.320). This level reflects the maximum application rate found on pesticide product labels and following processing of sugar cane or sugar beets, the residue levels of glutaraldehyde decrease to 1.72 ppm. Therefore, the Agency has no risk concerns from the food uses of glutaraldehdye, as indicated by the application rates and measured pesticide residue for this exposure scenario.

c. Dietary Risk from Drinking Water

There are no antimicrobial uses associated with glutarladehyde that are expected to significantly impact either surface or groundwater resources.

6. Residential Risk Assessment

Residential exposure to glutaraldehyde can occur from the antimicrobial uses of glutaraldehyde. The residential exposure assessment considers all potential pesticide exposure, other than exposure due to residues in food and drinking water. Exposure may occur during and after application methods including painting via brush/roller and airless sprayer. Each route of exposure (dermal, inhalation) is assessed, where appropriate, and risk is expressed as a Margin of Exposure (MOE), which is the ratio of estimated exposure to an appropriate No Observed Effect Level (NOAEL) dose. Based on the application methods, glutaraldehyde has been assessed for the residential mixing/loading/applicator (or handler) exposure.

a. Residential Toxicity

The toxicological endpoints and associated uncertainty factors used for assessing the non-dietary, residential and occupational risks for Glutaraldehyde are listed in Table 10. A MOE greater than or equal to 10 is considered adequately protective for the residential exposure assessment for the dermal route of exposure. The MOE of 100 includes 3x for inter-species extrapolation, 3x for intra-species variation. A MOE greater than or equal to 30 is considered adequately protective for the residential exposure assessment for the inhalation routes of exposure. The MOE of 100 includes 3x for inter-species extrapolation, 10x for intra-species variation. The Agency used the reference concentration (RFC) approach rather than the MOE approach for the inhalation risk assessment. Therefore, concentrations less that the RFC will be considered to be not of concern.

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Table 10. Glutaraldehyde Toxicological Endpoints Used for Occupational and Residential Assessment Exposure Scenario

Dose Used in Risk Assessment UF Study and Toxicological Effects

Dermal Exposures Short Term Irritation NOAEL = 50

mg/kg/day (2.5% percent a.i.)

10 Rat 28 day dermal toxicity study (MRID 43259101). LOAEL = 100 mg/kg/day (5.0% a.i.) based upon erythema, edema and skin lesions.

Intermediate Term

N/A N/A N/A

Long Term N/A N/A N/A Inhalation Exposures

Short Term Occupational (8 hours/day)

NOAEL = 0.7 mg/m3 HECocc = 0.041 mg/m3 RfCocc = 0.0013 mg/m3 (0.32 ppb*)

30 Two-week inhalation toxicity study in rats and mice (NIH pub 93-3348). LOAEL = 2.0 mg/m3 based upon histo-pathological alterations of the nasal passages, larynx, trachea and lung.

Short Term Residential (24 hours/day)

NOAEL = 0.7 mg/m3 HECres = 0.014 mg/m3 RfCres = 0.0005 mg/m3 (0.12 ppb*)

30 Same as above.

Intermediate Term Occupational (8 hours/day)

NOAEL = 0.51 mg/m3 HECocc = 0.03 mg/m3 RfCocc = 0.001 mg/m3 (0.24 ppb*)

30 Thirteen week inhalation toxicity study in rats and mice (NIH pub 93-3348). LOAEL = 1.02 mg/m3 based upon histo-pathological changes of the nasal and respiratory tract epithelium.

Intermediate Term Residential (24 hours/day)

NOAEL = 0.51 mg/m3 HECres = 0.01 mg/m3 RfCres = 0.0003 mg/m3 (0.073 ppb*)

30 Same as above.

Long Term Occupational (8 hours/day)

LOAEL = 0.26 mg/m3 HECocc = 0.019 mg/m3 RfCocc = 0.00006 mg/m3 (0.015 ppb*)

300 Two -Year inhalation toxicity study in rats and mice (MRID 448422-02). LOAEL = 0.26 mg/m3 based upon squamous epithelial hyperplasia/inflammation and turbinate necrosis.

Long Term Residential (24 hours/day)

LOAEL = 0.26 mg/m3 HECres = 0.004 mg/m3 RfCres = 0.00002 mg/m3 (0.005 ppb*)

300 Same as above

* Unit Conversion: ppb = (mg/m3 x 24.45 x 1000 ug/mg) / mw. For glutaraldehyde: 1 ppb = 0.00409 mg/m3

b. Comparison to Other Endpoints

The American Conference of Governmental Hygienists (ACGIH) has evaluated the glutaraldehyde literature and recommended a threshold limit value (TLV) of 0.2 mg/m3 (50 ppb) as a ceiling (C) value. A TLV-Ceiling is an exposure limit that should not be exceeded at any time during the workday and is normally assessed as a 15 minute exposure. Although the ACGIH did review the same animal toxicity studies that were used by EPA, the ACGIH chose a ceiling value because the literature indicated that short term exposures at or below 100 ppb resulted in symptoms of nose, throat, skin and eye irritation among medical workers using glutaraldehyde. The TLV-Ceiling for glutarladehyde was not based on the same methodology that EPA uses to establish RfCs.

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c. Residential Handler Exposure

i. Summary of Registered Residential Uses

Most glutaraldehyde-containing products are intended for use only in industrial or medical areas. However, the residential population may be exposed to household items such as laundry detergents and paints that have been treated with glutaraldehyde as a materials preservative (e.g., a slimicide). Table 11 identifies the residential exposure scenarios assessed for glutaraldehyde and also lists the application rates and methods for each scenario.

Table 11. Glutaraldehyde Residential Exposure Scenarios Use Exposure Scenario Exposure

Duration Exposure Pathway

Application Rate (ppm)

Material Preservation of Laundry Detergent

Handler Exposure While Using Treated Laundry Detergent Short Term

Dermal and Inhalation 100 to 1000

Material Preservation of Latex Paint

Handler Exposure While Using Treated Paint Short Term

Dermal and Inhalation

100 to 1000 Post Application Exposure to Treated Paint Short Term Inhalation

ii. Residential Exposure Assumptions

The residential handler exposures for the use of paint and laundry detergent treated with glutaraldehyde were assessed to determine dermal and inhalation exposures. Glutaraldehyde has a relatively high vapor pressure (0.3 mm Hg at 20o C), therefore, the unit exposure data from PHED are not applicable because these data are generally based upon chemicals that have a much lower vapor pressure (less than 1.0 x 10-4 mm Hg). When the vapor pressure is less than 1.0 x 10-4mm Hg, chemicals are airborne primarily as aerosols, while at higher vapor pressures, chemicals are airborne primarily as vapors. In addition, the toxicology endpoints were derived from inhalation studies where the test animals were exposed to glutaraldehyde vapor.

iii. Residential Handler Risk Assessment

Residential Handler Paint Inhalation Exposures

Residential handler inhalation exposure can occur when residents apply house paints that were treated with Glutaraldehyde as an in-can preservative at a rate of 100 ppm to 1000 ppm. The Agency used the EPA Wall Paint Exposure Model (WPEM) to estimate air concentrations resulting from these uses. When using the WPEM model with default assumptions, the 24 hour average air concentrations of 2.2 at the low rate or 22 ppb at the high rate exceed the short term RfC of 0.12 ppb and the inhalation exposures are of concern (Table 12).

In addressing public comments, limitations of the WPEM model were identified and an alternative method of assessing paint exposures using the box model approach (Landenburger,

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2007b) was proposed. The results of the box model assessment indicate that the glutaraldehyde exposure of 1.0 ppb exceeds the RFC at the highest application rate of 1000 ppm and is of concern. The glutaraldehyde exposure of 0.10 ppb at the lowest application rate does not exceed the RfC and is not of concern (Table 12).

Table 12. Short-Term Inhalation Risk Summary for Residential Painters Assessment

Method Used Application

Rate Time Spent

Painting (hrs)

Painted Surface Area (ft2)

Air Exchange Rate per hour

24-hour ADCD

Short Term RfC

WPEM Model 3.42 452A 0.45 22 ppb

Box Model 1000 ppm

1.5 353B 0.5C 1.0 ppb

WPEM Model 3.42 452A 0.45 2.2 ppb

Box Model 100 ppm

1.5 353B 0.5C 0.10 ppb

0.12 ppb

A. Assuming the walls of one room are painted as specified in the RESDIY scenario of WPEM. B. Assuming the walls of a 12x12x 8 room are painted minus the area of one door and one window. C. 1.0 air change per hour times a factor of 0.5 to account for imperfect mixing. D. The 24 hour average daily air concentration experienced by the residential painter on the day of painting.

Air concentrations in bold font indicate risks of concern because they exceed the RfC.

Result Comparison and Risk Characterization for Residential Handler Paint Inhalation Exposures

The Box Model assessment provided by the registrant indicates that exposures to glutaraldehyde are 22 times less than the exposures predicted by WPEM. Some of this difference can be explained by the different assumptions used such as time spent painting (WPEM = 3.4 hours, Dow = 1.5 hours) and the painted surface area (WPEM = 452 ft2, Dow = 353 ft2) which reduce the exposure. Other differences such as the assumption of living space volume (WPEM = 15583ft3, Dow = 6890 ft3) increase exposure. The remaining assumptions such as the air exchange rates and daily activity patterns are nearly identical. The most important input that creates a difference in the estimated exposures, however, is the glutaraldehyde emission rate. The WPEM model estimates this rate using two equations that are based upon chamber data collected for propylene glycol, ethylene glycol, butoxyethoxyethanol and texanol while the Dow assessment estimated this rate based upon chamber emission data for Bioban CS-1246. As shown in Table 13 below, Bioban has a higher vapor pressure (VP) and Henrys law constant (HLC) than the chemicals used in the WPEM model or glutaraldehyde which indicates that it would evaporate from the paint at a higher rate. This suggests that glutaraldehyde exposures predicted using Bioban emission data are overestimates of actual glutaraldehyde exposures.

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Table 13. VP and HLC Comparison of WPEM Chemicals, Bioban and Glutaraldehyde Chemical CAS # Molecular

Weight Vapor Pressure

(mm Hg) Henrys Law Constant

(Pa-m3/mol) Propylene Glycol* 57-55-6 76.1 0.13 0.0013 Ethylene Glycol* 107-21-1 62.1 0.092 0.006 Butoxyethoxyethanol* 112-34-5 162.2 0.02 0.0013 Texanol* 25265-77-4 216 0.0019 Bioban CS-1246 7747-35-5 143 4.4 0.084 Glutaraldehyde 111-30-8 100.1 0.3 0.006 *These chemicals are used in the WPEM Model.

Residential Handler Laundry Detergent and Fabric Softener Inhalation Exposures

The Agency used the EPAs Consumer Exposure Module (CEM) to estimate air concentrations resulting from the use of laundry detergent preserved with glutaraldehyde. Detailed information and the executable model can be downloaded from http://www.epa.gov/opptintr/exposure. For this exposure assessment, the CEM default scenario for the laundry detergent was the model of choice. This scenario assumes that the homeowner is exposed to the chemical in laundry detergent when using the laundry detergent in the utility room of a house and subsequently throughout the house for a 24-hr TWA. The results of the CEM model runs with default and updated assumptions are included in Table 11 and the model run details are included in Appendix B. The 24 hour TWAs range from 0.17 ppb to 7.5 ppb for the laundry detergent scenario depending upon the application rate and assumptions used and all exceed the short term RfC. The 24 hour TWAs exceed the RFC for the fabric softener scenario only at the maximum rate of 1000 ppm and are not of concern at the minimum rate of 100 pp (Table 14).

In addressing public comments, the limitations of the CEM model were identified and alternative methods of assessing laundry detergent exposures using the CEM model with modified inputs to correct the limitations were proposed. The most important limitation is that the inhalation exposure routine of CEM does not account for the dilution of the product in the wash water. Another limitation is that the assumption of 400 grams per load is outdated because detergents are now more concentrated. Alternative input parameters for the grams loaded were suggested; a value of 137 grams for laundry detergent and a value of 44 grams for fabric softeners. These values were based upon measured weights of selected detergent and fabric softener products.

Residential handler exposures to laundry detergent was reassessed using the CEM model with updated inputs for the amount of detergent used per day and also added an assessment of fabric softener exposures. Although a value of 137 grams was used for laundry detergent in the proposed assessment, a value of 200 grams was used because at least one major brand of laundry detergent is sold in 100 ounce containers which are advertised to treat 32 medium sized loads or 16 large size loads. When using the CEM model with the modified weight fraction to account for the wash water dilution and updated inputs, the 24 hour TWA Exposure of 0.019 ppb for the laundry detergent scenario does not exceed the RfC (Table 14). This assessment is also protective for fabric softeners because the amount of fabric softener used per load is less than amount of laundry detergent used.

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Table 14. Inhalation Risks for Laundry Detergent and Fabric Softener Handlers EFAST

Assessment Method

Weight Fraction

(ppm)

Amount of Laundry Detergent Used Per Day/

Duration of Use

Air Exchange Rate per hour

24-hour TWAF

Short Term RfC

Laundry Detergent

Default Assumptions 1000

A 400 grams/0.667 hoursC

0.45

7.5 ppb

0.12 ppb

Default Assumptions 100

A 400 grams/0.667 hoursC 0.75 ppb

Updated Assumptions 1000

A 200 grams/0.667 hoursD 3.7 ppb

Updated Assumptions 100

A 200 grams/0.667 hoursD 0.37 ppb

Modified Weight Fraction 1.5

B 137 grams/0.417 hoursE 0.019 ppb

Fabric Softener

Updated Assumptions

1000A 50 grams/0.667 hoursG 0.45

0.93 0.12 ppb

100A 0.093 A. Weight fraction = The amount of GA in the laundry detergent. B. Weight fraction = (137 ml of detergent containing 1000 ppm GA/ 92 liters of wash water) C. Default assumptions as listed in the CEM Model documentation. D. Updated assumption based upon more concentrated detergent formulations. E. Assumptions used in the registrant assessment (Finking and McCready, 2007a). F. The 24 hour TWA air concentration experienced by the laundry detergent handler on the day of detergent use.

*Air concentrations in bold font indicate risks of concern because they exceed the RfC.

Result Comparison and Risk Characterization for Residential Handler Laundry Detergent and Fabric Softener Inhalation Exposures

The Modified CEM assessment indicates that exposures to glutaraldehyde are 400 or 200 times less than the exposures predicted by the default or updated CEM assessments. Some of this difference can be explained by the different assumptions used such as the amount of product used (default = 400 grams, updated = 200 grams, modified = 137 grams) and the event duration (default = 0.667 hours, modified = 0.417 hours). The largest source of the difference is the weight fraction which is 1000 ppm for the default and updated assessments and 1.5 ppm for the modified assessment.

Residential Handler Dermal Exposures

The residential handler dermal exposures to glutaraldehyde were assessed by comparing the concentrations in the paints and the laundry detergents with the concentrations used in the dermal toxicity studies. This comparison is shown in Table 15 and indicates that the dermal exposures are not of concern at the maximum application rate of 1000 ppm (0.1 percent) because the Margin of Exposure (MOE) of 25 exceeds the target MOE of 10.

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Table 15. Residential Handler Dermal Exposures Application Rate

(ppm) Application Rate

(Percent) Glutaraldehyde

NOAEL NOAEL

ConcentrationA MOEB

(Target MOE = 10) 1000 0.1 50 mg/kg/day 2.5% 25

A. The concentration of glutaraldehyde in the test solution applied at the NOAEL dose. B. MOE = NOAEL Concentration (percent) / Application Rate (percent)

d. Residential Post-application Assessment

i. Residential Post-application Exposure Assessment

The Wall Paint Exposure Model (WPEM) was used to estimate air concentrations resulting from the use of paint preserved with GA. The default assumptions from the WPEM RESADULT scenario were used. This scenario assumes that the home occupants are exposed to the chemical in paint in adjacent rooms (Zone 2) during painting and in the painted room (Zone 1) after painting. This scenario includes 7 hours in Zone 2, 8 hours in Zone 1 and 6 hours outside of the house.

In addressing public comments, the limitations of the WPEM model were reiterated and additional concerns that some of default assumptions included in the WPEM residential post application scenario are also unrealistic. The most important point of these assumptions is that a coat of primer would be applied immediately prior to the finish coat. The registrants contend that primer coats are only applied during extensive remodeling and that the residents would not be expected to be in Zone 1 for eight hours immediately following the painting because the room would not be ready for occupancy. Given these factors, the registrants did not submit a box model assessment of post application exposures for comparison to the WPEM assessment.

Since painting only occurs on an episodic basis and because the glutaraldehyde evaporates fairly quickly from the paint, only short term exposures were assessed. As was done for the residential handler assessment discussed previously, the WPEM model was set to run at one minute intervals for one 24 hour day with an exposure event frequency of 27,375 exposure events per lifetime to yield a 24 hour average daily concentration (ADC) that includes only the day of painting for comparison to the short term RfC. The air concentrations are given in Table 16 and exceed the RfC.

Table 16. Post Application Risk Summary for Glutaraldehyde Treated Paint Assessment

Method Application

Rate Area

Painted Air

Exchange Rate

C24 in Zone 1 (ppb)

C24 in Zone 2 (ppb)

24 Hour TWA A (ppb)

Short Term RfC

(ppb)

WPEM 1000 ppm 452 ft2

(one room) 0.45 ACH 97 33 37 0.12

100 ppm 9.7 3.3 3.7 A. TWA air concentration experienced by the resident person for the first 24 hours during and after painting.

Air concentrations in bold font indicate risks of concern because they exceed the RfC.

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ii. Residential Post-application Risk Characterization

The 24 Hour TWA of 37 ppb calculated by the WPEM model for the post application scenario where the resident is not in the room during painting is greater than the 24 Hour TWA of 22 ppb that was calculated by WPEM for the residential handler scenario where the resident is in the room during painting. The primary reason for this difference is that 3.4 gallons of paint is applied during the post application scenario while only 1.1 gallons of paints are applied during the handler scenario. If it is assumed that the residents are not in the painted areas of the residence immediately following application of the primer and top coat then the post application exposures predicted by WPEM can be considered to be irrelevant.

7. Aggregate Risk Assessment

The Food Quality Protection Act amendments to the Federal Food, Drug, and Cosmetic Act (FFDCA, Section 408(b)(2)(A)(ii)) require that there is a reasonable certainty that no harm will result from aggregate exposure to pesticide chemical residue, including all anticipated dietary exposures and other exposures for which there are reliable information. Aggregate exposure typically includes exposures from food, drinking water, residential uses of a pesticide, and other non-occupational sources of exposure.

An aggregate risk assessment was not conducted for glutaraldehyde. The dietary, dermal and inhalation endpoints are all based upon different studies and toxicological effects. There are no incidental oral exposure scenarios identified for glutaraldehyde. On this basis, no aggregation of exposures was performed and risks are as expressed for each scenario identified in the risk assessment for glutaraldehyde.

8. Occupational Risk

a. Occupational Toxicity

The toxicological endpoints used in the occupational handler assessment of glutaraldehyde can be found in Table 10, Residential and Occupational Toxicological Doses and Endpoints for glutaraldehyde, of this document.

b. Occupational Handler Exposure Assumptions

Occupational risk for all potentially exposed populations is measured by a Margin of Exposure (MOE), which determines how close the occupational exposure comes to a No Observed Adverse Effect Level (NOAEL) from toxicological studies. Occupational risk is assessed for exposure at the time of application (termed handler exposure). Application parameters are generally defined by the physical nature of the formulation (e.g., formula and packaging), by the equipment required to deliver the chemical to the use site and by the application rate required to achieve an efficacious dose. The Agency evaluated representative occupational scenarios using the application rates as recommended on glutaraldehyde product labels.

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c. Occupational Handler Exposures

Occupational Handler Scenarios

The term handler applies to individuals who mix, load, and apply pesticide products. There are several occupational handler exposure scenarios that involve glutaraldehyde products. These scenarios include: open pouring of products into industrial processes, automatic addition of products into industrial processes, mopping animal and poultry housing, spraying or fogging animal and poultry housing, applying RTU spray to non-critical hard surfaces in medical areas, applying RTU wipes to non-critical hard surfaces in medical areas and connecting medical waste collection devices that contain glutaraldehyde.

Occupational Handler Exposure Assessment Rationale

Glutaraldehyde dermal irritation exposures and risks were not estimated for occupational handler exposures. Rather, dermal irritation exposures and risks will be mitigated using default personal protective equipment (PPE) requirements based on the toxicity of the end-use product. To minimize dermal exposures, the minimum PPE required for mixers, loaders, and others exposed to end-use products containing concentrations of glutaraldehyde will be long-sleeve shirt, long pants, shoes, socks, chemical-resistant gloves, and chemical-resistant apron. Note that chemical-resistant eyewear will be required if the end-use product is classified as category I or II for eye irritation potential.

Glutaraldehyde has a relatively high vapor pressure (0.3 mm Hg at 100% solution concentration), therefore, the unit exposure data from PHED and CMA are not applicable because these data are generally based upon chemicals that have a much lower vapor pressure (less than 1.0 x 10-4 mm Hg). When the vapor pressure is less than 1.0 x 10-4mm Hg, chemicals are airborne primarily as aerosols, while at a higher vapor pressure, chemicals are airborne primarily as vapors. There are 5 glutaraldehyde replicates in the CMA dataset, however, and they are summarized in Table 17. The CMA data is of limited usefulness because the limit of detections were very high due to the short sampling times and limitations of the adsorbent tube method that was used. However, based on these data, the air concentrations for occupational handlers exceed the RfC and are of concern.

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Table 17. Summary of Glutaraldehyde Air Concentration Data from the CMA Study CMA Rep

Use Operation Monitored Amount Handled During Monitoring

Sample Duration (minutes)

GA Air Concentration

(ppb) 54 Cooling Tower Liquid Pour from 55

gallon drum 504 lbs of a 45% product

5

Table 18. Glutaraldehyde Air Concentrations During Endoscopy Disinfection

Study Operation Solution Strength Sample Type GA Air

Concentration (ppb)

Comments

Binding and Witting, 1990

Disinfection in operating theatres

0.025% Peak 8 hr TWA

30 10

0.15% Peak 8 hr TWA

570 100

Leinster, Baum and Baxter, 1993

Cold Sterilization in English Hospitals

STEL

Table 19. Glutaraldehyde Air Concentrations Measured During Industrial Operations Location Operation Solution

Strength Sample Type

Sampled Period

(minutes)

GA Air Concentration

(ppb)

Source

Latex Plant Addition to truck sump 45% PBZ 15 27 SIDS (CA) Paper Mill 3 feet above wire at Area ND SIDS (GA) machine #3 Paper Mill 1 foot above machine chest Area 15 ND - 220 UCC, (Canada) opening at various addition (LOD=20) 1998

rates Paper Mill Above blend and machine Area 15 ND (n=5) UCC (Kent UK) chests at various addition (LOD=30) 1998

rates Paper Mill Pumping biocides at 50% Area 60 4 - 130 SIDS (Belgium) various locations Paperboard Various Locations 50% Area 30-60 ND - 1.8 (n=18) SIDS Mill throughout process Drilling Field Addition to drilling mud Aldacide 20 - 120 (n=9) SIDS (BP Alaska) G Aluminum Hot Rolling - Air in metal 45% Area 30 6 - 122 SIDS Mill working fluid sump Aluminum Mill floor during rolling Uconex Area 15 ND SIDS Rolling Plant Inside covered sump 345 Area 15 122 - 175 (n=2) SIDS Breakdown Adjacent to spray nozzles Area 15 6 - 8 (n=3) SIDS Mill near operators Aluminum Addition areas over tanks Not Area 15 ND - 180A (n=23) UCC, Hot Rolling near rolling mill Reported (LOD = 46) 1994 Mill (NE US) Walking around in mill PBZ 15

d. Occupational Handler Exposure and Risk Assessment

Most of the available exposure data are from short term samples of approximately 15 minutes in duration and they were taken as a comparison to the ACGIH TLV-Ceiling of 50 ppb. Although many of the short term samples exceeded the RfC of 0.32 ppb, these samples are not comparable to the RfC because the un-sampled periods probably had lower exposures than the sampled period.

i. Professional Painter Inhalation Exposure Assessment

The Agency used the EPA Wall Paint Exposure Model (WPEM) to estimate air concentrations resulting from the use of paint preserved with glutaraldehyde. The professional painter inhalation exposure to GA vapors during painting with GA treated paint was assessed using the WPEM Model. The WPEM default scenario (RESPROF) for the professional painter was used and this scenario assumes that two professional painters are exposed to a chemical in paint while painting an entire apartment in a work day. The WPEM model was set to run at one minute intervals for the duration of the work day with an exposure event frequency of 27,375 exposure events per lifetime to yield an 8 hour time weighted average (TWA) that includes only the day of painting for comparison to the short term RFC. The results of modeling runs are included in Appendix B and the risks are summarized in Table 17. Because the 8 hour TWA air concentrations exceed the short term RfC of 0.32 ppb, the inhalation exposures are of concern at both the maximum and minimum application rates. The C15-min air concentrations also exceed the TLV-Ceiling of 50 ppb Table 20).

In addressing public comments, limitations of the WPEM model were identified and an alternative method of assessing paint exposures using the box model approach (Landenburger, 2007a) was provided. The box model assessment of the occupational painter scenario (Landenberger 2007a) is similar to the box model assessment of the residential handler scenario discussed previously. One major difference is that a fixed release rate was used instead of the variable release rate that was used for the more refined residential handler assessment. The other major difference is that only one zone was used for the occupational handler assessment while two zones were used for the residential hander assessment. The results of the Box model assessment are included in Table 20 and indicate that the glutaraldehyde exposures exceed the RFC at both the maximum and minimum application rates and are of concern.

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Table 20. Inhalation Risk Summary for Occupational Painters Method Painted Surface

Area Air Exchange Rate

Hours per Day

C15-minA (ppb)

ACGIH TLV-C (ppb)

C-8hourB (ppb)

Short Term RfC (ppb)

Maximum Application Rate = 1000 ppm WPEM 2131 ft2

(one apartment) 0.45 ACH 8

690 50

530 0.32 Box Model 2130 ft2

(6 standard rooms) 0.5 ACHC 7.6

Minimum Application Rate = 100 ppm WPEM 2131 ft2 0.45 ACH

8 69

50 53

0.32 Box Model 2130 ft2 0.5 ACHC 0.76 A. Maximum 15 minute average air concentration. B. Maximum 8 hour time weighted average air concentration on the day of painting assuming one hour for lunch. C. 1.0 air change per hour times a factor of 0.5 to account for imperfect mixing.

Air concentrations in bold font are of concern because they exceed the TLV-C and the Short Term RfC.

Risk Characterization for Professional Painter Inhalation Exposure

The Box Model assessment provided by the Dow Chemical Company indicates that occupational handler exposures to glutaraldehyde are 70 times less than the exposures predicted by WPEM. Most of the input values such as the painted surface area, air exchange rate are similar. As is the case for the residential handler assessment, the most important input that created a difference in the estimated exposures is the glutaraldehyde emission rate which was based on chamber testing of Bioban CS-1246 which has a higher vapor pressure and Henrys law constant than glutaraldehyde.

ii. Hard Surface Disinfectant Inhalation Exposure Assessment

Three glutaraldehyde-containing products (15136-9, 55195-3 and 55194-5) are used to disinfect non-critical hard surfaces in medical clinics, dental clinics and veterinary offices. Two of these products are RTU sprays and one is an RTU wipe. The Agency used the EPA CEM Model estimate air concentrations resulting from the use of glutaraldehyde in hard surface disinfectants. In addressing public comments, limitations of the CEM model were reiterated and an alternative method of assessing exposures using the chamber emissions data was provided together with the ConsExpo Model (McCready and Finking, 2007). A general purpose cleaner scenario of the CEM model was utilized to estimate air concentrations resulting from the use of gl